1. Field of the Invention
The present invention relates to a substrate for use in crystallizing polymeric compounds including biomolecules such as proteins, nucleic acids, and sugars; and resins, as well as other organic compounds and inorganic compounds, and to a method for producing the substrate.
2. Description of the Related Art
Three-dimensional structural analysis on organic polymers has been significantly important in order to elucidate the functions of these various organic polymers such as proteins. Particularly, in light of a fact that various diseases are induced by abnormality of proteins or the like, structural analysis on proteins which may induce various diseases has been carried out, and development of pharmaceuticals based on the analysis has been progressed in pharmaceutical fields. For instance, generally, structural analysis on proteins is performed by crystallizing purified protein solutions and subjecting the purified proteins to X-ray crystallographic analysis, NMR analysis, or a like analysis (see “The biochemical Experiment 1, Protein chemistry 1, Separation and Purification” edited by the Japanese Biochemical society, First Edition, vol. 1, published by Tokyo kagaku dozin Co., Ltd., published on Jul. 11, 1984, pp. 82-87; and “The Fourth Series of Experimental Chemistry 2, basic operation II” edited by the Chemical Society of Japan, Vol. 2, published by Maruzen Co., Ltd., published on Dec. 5, 1990, pp. 354-358). However, it is extremely difficult to set conditions for crystallization of proteins that enable to form single crystals while suppressing generation of micro crystals.
Particularly, as a contact area of a solution (liquid phase) containing a target protein with an interior of a crystallization apparatus (solid phase) is increased, crystal nuclei are likely to be generated on contact sites. As a result, it is highly likely that crystal polymorphs and micro crystals are generated, which makes it difficult to obtain crystals suitable for structural analysis.
To solve the above drawback, in recent years, crystallization in a microgravity space has been actually carried out in a space shuttle (“Dynamics on Crystal Growth, crystal growth from a solution”, by Kiyotaka SATOH, First Edition, Vol. 6, Kyoritsu Shuppan Co., Ltd, published on Sep. 1, 2002, pp. 67-69). However, crystallization in a microgravity space costs high, including installation cost, and accordingly, it is conceived that practice of crystallization in a microgravity space is extremely difficult.
As another measure for solving the drawback, Japanese Unexamined Patent Publication No. 2003-286100 proposes a technique of crystallizing proteins. The publication discloses that droplets of a protein solution to be crystallized are dropped on a substrate with use of a droplet ejector to form hemispherical microdots on the substrate, and that the hemispherical microdots are dried in a predetermined atmosphere for crystallizing the protein.
In the above method, since each of the droplets has a hemispherical shape, a contact area of the droplet with a substrate surface is relatively large. Accordingly, it is highly likely that crystal nuclei are generated on contact sites, with the result that crystal polymorphs or micro crystals are likely to be generated. Further, since drying progresses in a phase boundary between the hemispherical portion and a gas phase, isotropic drying of the droplets is hindered, which may likely to generate crystal polymorphs.